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Biological tissues, such as muscle, can increase their mechanical strength after swelling due to the existence of many biological membrane barriers that can regulate the transmembrane transport of water molecules and ions. Oppositely, typical synthetic materials show a swelling-weakening behavior, which always suffers from a sharp decline in mechanical strength after swelling, because of the dilution of the network. Here, we describe a swelling-strengthening phenomenon of polymer materials achieved by a bioinspired strategy. Liposomal membrane nanobarriers are covalently embedded in a crosslinked network to regulate transmembrane transport. After swelling, the stretched network deforms the liposomes and subsequently initiates the transmembrane diffusion of the encapsulated molecules that can trigger the formation of a new network from the preloaded precursor. Thanks to the tough nature of the double-network structure, the swelling-strengthening phenomenon is achieved to polymer hydrogels successfully. Swelling-triggered self-strengthening enables the development of various dynamic materials. The swelling-weakening behaviour of synthetic hydrogels is a major limitation to many applications. Here, the authors report on the covalent linkage of precursor loaded liposomes which are deformed upon hydrogel swelling and release precursor to form a secondary network strengthening the hydrogel.

The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. Microbiota transplantation is an important approach to prevent and treat disease as it can inhibit pathogen colonization and positively modulate bacterial composition. However, the development of oral bacterial therapeutics has been restricted by low bioavailability and limited retention in the gastrointestinal tract. Here, we report a simple yet highly efficient method to coat gut microbes via biointerfacial supramolecular self-assembly. Coating can be performed within 15 min by simply vortexing with biocompatible lipids. Bacteria coated with an extra self-assembled lipid membrane exhibit significantly improved survival against environmental assaults and almost unchanged viability and bioactivity. We demonstrate their enhanced efficacies in oral delivery and treatment using two murine models of colitis. We suggest that biointerfacial supramolecular self-assembly may provide a unique platform to generate advanced bacterial therapeutics for the treatment of various diseases. Oral microbiota delivery is an approach to treat and prevent disease but suffers from low retention and bioavailability. Here the authors report on a lipid coating to protect against environmental assault maintaining viability and bioactivity of the bacteria and demonstrate effective application in a colitis model.

Bacterial infection has become one of the leading causes of death worldwide, particularly in low‐income countries. Despite the fact that antibiotics have provided successful management in bacterial infections, the long‐term overconsumption and abuse of antibiotics has contributed to the emergence of multidrug resistant bacteria. To address this challenge, nanomaterials with intrinsic antibacterial properties or that serve as drug carriers have been substantially developed as an alternative to fight against bacterial infection. Systematically and deeply understanding the antibacterial mechanisms of nanomaterials is extremely important for designing new therapeutics. Recently, nanomaterials‐mediated targeted bacteria depletion in either a passive or active manner is one of the most promising approaches for antibacterial treatment by increasing local concentration around bacterial cells to enhance inhibitory activity and reduce side effects. Passive targeting approach is widely explored by searching nanomaterial‐based alternatives to antibiotics, while active targeting strategy relies on biomimetic or biomolecular surface feature that can selectively recognize targeted bacteria. In this review article, we summarize the recent developments in the field of targeted antibacterial therapy based on nanomaterials, which will promote more innovative thinking focusing on the treatment of multidrug‐resistant bacteria. To address the challenge of antibiotic‐resistant bacteria, nanomaterials‐mediated targeted bacteria depletion in either a passive or active manner has emerged as one of the most promising approaches for antibacterial treatment. In this review, we summarize the recent development in the field of targeted antibacterial therapy based on nanomaterials, which show advantages in increasing local concentration around bacterial cells to enhance inhibitory activity and reduce side effects. This work would promote more innovative thinking focusing on the treatment of multidrug‐resistant bacteria.

Bacteria have been extensively utilized for bioimaging, diagnosis and therapy given their unique characteristics including genetic manipulation, rapid proliferation and disease site targeting specificity. However, clinical translation of bacteria for these applications has been largely restricted by their unavoidable side effects and low treatment efficacies. Engineered bacteria for biomedical applications ideally need to generate only a low inflammatory response, show slow elimination by macrophages, low accumulation in normal organs, and almost unchanged inherent bioactivities. Here we describe a set of stealth bacteria, cell membrane coated bacteria (CMCB), meeting these requirement. Our findings are supported by evaluation in multiple mice models and ultimately demonstrate the potential of CMCB to serve as efficient tumor imaging agents. Stealth bacteria wrapped up with cell membranes have the potential for a myriad of bacterial-mediated biomedical applications. The use of engineered bacteria for biomedical applications is limited by side effects such as inflammatory response. Here the authors engineer cell membrane coated bacteria as in vivo tumor imaging agents, and show that these generate a lower inflammatory response and reduced macrophage clearance.

Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by low treatment efficacy, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers. Optimal bacteria conjugated with an average of 2.8 × 10 5 aptamers per cell present the highest specificity to tumor cells in vitro, separately generating near 2- and 4-times higher accumulation in tumor tissue at 12 and 60 hours compared to unmodified bacteria. In both 4T1 and H22 tumor-bearing mouse models, aptamer-conjugated attenuated Salmonella show enhanced antitumor efficacy, along with highly activated immune responses inside the tumor. This work demonstrates how bacterial behaviors can be tuned by surface conjugation and supports the potential of aptamer-conjugated bacteria for both targeted intratumoral localization and enhanced tumor biotherapy. Bacteria-based therapy has shown promise for cancer treatment. To enhance tumor accumulation, here the authors describe the design of tumor specific aptamer-conjugated bacteria, to improve intratumor localization and enhance therapeutic efficacy.

Methods capable of manipulating bacterial colonization are of great significance for modulating host-microbiota relationships. Here, we describe a strategy of in-situ chemical reaction-mediated covalent localization of bacteria. Through a simple one-step imidoester reaction, primary amino groups on bacterial surface can be converted to free thiols under cytocompatible conditions. Surface thiolation is applicable to modify diverse strains and the number of introduced thiols per bacterium can be easily tuned by varying feed ratios. These chemically reactive bacteria are able to spontaneously bond with mucous layer by catalyst-free thiol-disulfide exchange between mucin-associated disulfides and newly converted thiols on bacterial surface and show thiolation level-dependent attachment. Bacteria optimized with 9.3 × 10 7 thiols per cell achieve 170-fold higher attachment in mucin-enriched jejunum, a challenging location for gut microbiota to colonize. As a proof-of-concept application for microbiota transplantation, covalent bonding-assisted localization of an oral probiotic in the jejunum generates an improved remission of jejunal mucositis. Our findings demonstrate that transforming bacteria with a reactive surface provides an approach to chemically control bacterial localization, which is highly desirable for developing next-generation bacterial living bioagents. Transplantation of helpful bacteria has been used to treat disease through modulating host microbiota. Here, the authors report a strategy to control bacteria localization in the jejunum, via an in vivo in-situ thiol-disulfide exchange reaction between surface-reactive bacteria and mucous.

The skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials. It is desirable to be able to mimic the properties of skin with hydrogels, but challenging to achieve. Here, the authors report the use of functionalised extracellular vesicles as crosslinkers for skin-mimicking hydrogels with good mechanical strength.

Despite immunosuppression is critical for reducing immune overactivation, existing immunosuppressive agents are largely restricted by low inhibition efficiencies and unpredictable off‐target toxicities. Here, the use of the dopaminergic system is reported to suppress hyperactive immune responses in local inflamed tissues. A polydopamine nanoparticular immunosuppressant (PDNI) is synthesized to stimulate regulatory T (Treg) cells and directly inhibit T helper 1 (Th1), Th2, and Th17 cells. Moreover, PDNI can inhibit the activation of dendritic cells to upregulate the ratio of Treg/Th17, which assists the reversion of inflammatory responses. The application of dopaminergic immunoregulation is further disclosed by combining with gut microbiota modulation for treating inflammations. The combination is implemented by coating living beneficial bacteria with PDNI. Following oral delivery, coated bacteria not only suppress the hyperactive immune responses but also positively modulate the gut microbiome in mice characterized with colitis. Strikingly, the combination demonstrates enhanced treatment efficacies in comparison with clinical aminosalicylic acid in two murine models of colitis. The use of the dopaminergic system opens a window to intervene immune responses and provides a versatile platform for the development of new therapeutics for treating inflammatory diseases. The dopaminergic system is reported to suppress hyperactive immune responses in local inflamed tissues by a polydopamine nanoparticular immunosuppressant, which can stimulate regulatory T lymphocytes and dendritic cells, while directly inhibit T helper cells. The application of dopaminergic immunoregulation is further disclosed by combining with oral probiotics that can modulate the gut microbiota for treating colitis.

Breakthroughs in the field of nanotechnology, especially in nanochemistry and nanofabrication technologies, have been attracting much attention, and various nanomaterials have recently been developed for biomedical applications. Among these nanomaterials, nanoscale titanium dioxide (nano-TiO2) has been widely valued in stomatology due to the fact of its excellent biocompatibility, antibacterial activity, and photocatalytic activity as well as its potential use for applications such as dental implant surface modification, tissue engineering and regenerative medicine, drug delivery carrier, dental material additives, and oral tumor diagnosis and treatment. However, the biosafety of nano-TiO2 is controversial and has become a key constraint in the development of nano-TiO2 applications in stomatology. Therefore, in this review, we summarize recent research regarding the applications of nano-TiO2 in stomatology, with an emphasis on its performance characteristics in different fields, and evaluations of the biological security of nano-TiO2 applications. In addition, we discuss the challenges, prospects, and future research directions regarding applications of nano-TiO2 in stomatology that are significant and worthy of further exploration.

The mucosal barrier consisting of physicochemical, immune, and microbial components is the first line of defense against external stimuli. Breakdown of the mucosal barrier causes the occurrences of various diseases, while methods capable of multifacetedly restoring mucosal barrier functions have been rarely reported. Here, we describe the restoration of the physicochemical, immune, and microbial homeostasis of the mucosal barrier by in situ formation of a living-synthetic therapeutic coating (LSTC). Through metal-phenolic complexation and π-π stacking interactions, ethyl gallate can chelate Bi III ions to form an adhesive coating on mucosal surfaces, which enables further hybridization with living bacteria. Due to the beneficial effects of Bi III and ethyl gallate and the probiotic characteristic of carried bacteria, LSTC increases the barrier integrity, mitigates mucosal inflammation, and maintains normal homoeostasis of the microbiota. In two murine models of aerobic vaginitis and vaginal candidiasis, LSTC demonstrates the potency to alleviate vaginal pathological injury and decrease vaginal inflammatory infiltration. Vaginal infections influence about 75% of adult women worldwide each year. Here, the authors report a strategy to treat vaginal infection by restoring the homeostasis of the vaginal mucosal barrier through in situ formation of a living-synthetic therapeutic coating.